Papillary thyroid carcinoma (PTC) arising in patients exposed to ionizing radiation in childhood (e.g., post-Chernobyl) predominantly carries which molecular alteration?
- A BRAF V600E point mutation in >60% of cases
- B NRAS codon 61 mutation with concurrent TERT promoter mutation
- C RET/PTC rearrangements (chromosomal inversions/translocations creating RET fusion oncogenes) ✓
- D ALK gene rearrangement producing ALK fusion proteins
Explanation
Post-radiation PTC (especially childhood radiation exposure — Chernobyl, therapeutic neck irradiation) is characterized by a high prevalence of RET/PTC chromosomal rearrangements (RET gene on 10q11.2 fused to various partner genes — RET/PTC1 involving H4/CCDC6; RET/PTC3 involving NCOA4). These inversions are caused by double-strand DNA breaks induced by ionizing radiation, with rejoining of RET to partner genes on the same chromosome. The resulting fusion oncoproteins constitutively activate the MAPK and PI3K/AKT pathways. BRAF V600E is the most common alteration in sporadic adult PTC (~60%) but is less frequent in radiation-associated PTC; NRAS mutations with TERT promoter mutations suggest follicular-variant PTC or poor-prognosis PTC; ALK rearrangements are rare in thyroid carcinoma.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.